Schizophrenia is a chronic, severe, and disabling brain disorder that has been recognized throughout recorded history. It affects about 1 percent of the population. The distressing symptoms and the deterioration and decline associated with schizophrenia make it one of the most severe mental illnesses from which a patient can suffer. Although the true etiology of schizophrenia remains unknown, a substantial body of research suggests that dopamine plays a key role in its pathophysiology.
Schizophrenia is a syndrome characterized by three clusters of symptoms including positive symptoms in the form of hallucinations and delusions, negative symptoms such as anhedonia and poverty of speech, and cognitive impairment, especially memory and executive functions. It is a debilitating mental illness that typically strikes in early adolescence and leads to major deterioration in social and vocational functions.
In schizophrenia there is an increase in dopamine transmission between the substantia nigra to the caudate nucleus-putamen (neostriatum) compared with normal. Dopamine transmission, however, is reduced in other dopaminergic pathways, such as in the mesolimbic forebrain and the tubero-infundibular system. The dopamine hypothesis of schizophrenia proposes that increased levels of dopamine or dopamine receptors in the dorsal and/or ventral striatum underlie this disorder.
Available antipsyotics (neuroleptics) both typical and atypical are efficacious in treating positive symptoms of schizophrenia. However, these drugs may cause serious side effects, some of which may be irreversible, such as, tardive dyskinesia. Additionally many patients fail to respond adequately to neuroleptics and may develop residual symptoms with functional and social impairment. About 30% of patients show treatment resistance to neuroleptics and continue to have moderate to sever positive symptoms. These treatment resistant patients require the addition of other medications. Most of the available medications for treating schizophrenia have minimal to no effect on negative symptoms and cognitive functions, a problem that is currently the focus of medication development in schizophrenia. Because of the shortcomings of the currently available treatments there is a search for other more effective methods of treatment.